Human plasma contains cross-reactive Abeta conformer-specific IgG antibodies.
Two conformers of aggregated Abeta, i.e., fibrils and oligomers, have been deemed important in the pathogenesis of Alzheimer's disease. We now report that intravenous immune globulin (IVIG) derived from pools of human plasma contains IgGs that recognize conformational epitopes present on fibrils and oligomers, but not their soluble monomeric precursor. We have used affinity chromatography to isolate these antibodies and have shown that they cross-reacted with comparable nanomolar avidity with both types of Abeta aggregates; notably, binding was not inhibited by soluble Abeta monomers. Our studies provide further support for investigating the therapeutic use of IVIG in Alzheimer's disease.
O'Nuallain
Brian
B
Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee 37920, USA.
Acero
Luis
L
Williams
Angela D
AD
Koeppen
Helen P McWilliams
HP
Weber
Alfred
A
Schwarz
Hans P
HP
Wall
Jonathan S
JS
Weiss
Deborah T
DT
Solomon
Alan
A
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D003429:Cross Reactions / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous